POINT-TOUCH TECHNIQUE OF BOTULINUM TOXIN INJECTION FOR THE TREATMENT OF SPASMODIC DYSPHONIA

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1 Ann Otol Rhinol LaryTlllolI01:1992 POINT-TOUCH TECHNIQUE OF BOTULINUM TOXIN INJECTION FOR THE TREATMENT OF SPASMODIC DYSPHONIA DAVID C. GREEN, MD SEAlTLE, WASHINGTON PAUL H. WARD, MD Los ANGELES, CALIFORNIA GERALD S. BERKE, MD LosANGELES,CALIFORNIA BRUCER.GERRATT,PHD LosANGE~,CALIFORNIA Intralaryngeal injections of botulinum toxin (Botox), under electromyographic guidance, have emerged as an effective treatment for adductor spasmodic dysphonia. To remain effective, these injections must be repeated every 3 to 9 months as the symptoms recur. One drawback to the currentmethod is the need for electromyographic confirmationofneedle placementinto the thyroarytenoid muscle. This report describes an anatomic approach to Botox injection that requires only flexible nasopharyngeal endoscopy and careful evaluation of the anatomic landmarks. This technique has been used successfully on 13 patients, and objective pretreatment and posttreatment measures are reported. KEY WORDS - botulinum injection, laryngeal dystonia, spastic dysphonia. INTRODUCTION Spasmodic dysphonia is a serious voice disorder characterized by a strained or strangled voice, and it often interrupts the fluency of continuous speech. Since the first descriptionofthe disorderby TraubeI in 1871, its exact cause and treatment have been the subject of controversy. In the past, this disorder was thought to reflectpsychiatric problems. More recently, Blitzeret a1 2 found through clinical and electromyography (EMG) evaluation that many patients with "spastic dysphonia" actually have a dystonia. Dystonia is a neurologic disorder of motor control processing characterized by abnormal, often action-induced,involuntarymovements or uncontrolled spasms. The cause is usually idiopathic. The dystonia may be restricted to the larynx or present in other areas of the body as well, such as blepharospasm.i There are a variety oftreatments for adductor spastic dysphonia, whichinclude speech therapy, psychotherapy, biofeedback, systemic medicine, nerve section, botulinum toxin (Botox) injection, and thyroplasty. Dedo'' was the first to describe recurrent laryngeal nerve section as a treatment for spastic dysphonia. The aim was to achieve a voice that was slightly breathy but easier to produce. After a 3-year follow-up, his group" reported a 10% to 15% recurrence rate according to patient self-evaluations. Aronson and DeSantoS reported an initial success rate of97% at 6 months for recurrentlaryngeal nerve section. This success rate fell to 36% at 3 years' follow-up. The failures showed gradual hyperadduction oftheintactvocal fold againstthe paralyzed fold. This was thought to be due to a worsening of the patient's underlying neurologic condition. Biller et al 6 reported, in 1979, crushing the recurrent laryngeal nerve as a treatment for spastic dysphonia. Although all patients had initial improvement, only 13% were improved at 3 years' followup,? Blitzer et al 8,9 reported the first series of patients with focal laryngeal dystonia to be treated with local vocal fold injectionofbotox. Thistoxin acts presynaptically at nerve terminals to prevent calcium-dependent release of acetylcholine, which results in muscle paralysis. There were five patients in their series, and all, within 2 to 3 days, experiencedbenefit that lasted 3 to 6 months. Although the authors initially injected only one vocal fold, they now perform bilateral injections. Therewereno systemic side effects from the injections, but they state that the long-term systemic or local laryngeal effects are unknown. Using EMG, Ludlow et al io studied patients with adductor spastic dysphonia who failed unilateral recurrent laryngeal nerve section. They found that some of the failures were due, at least in part, to reinnervation of the thyroarytenoid muscle by the previously sectioned recurrent laryngeal nerve, and that compensation by the nonoperated side may have From the Division ofhead and Neck Surgery, University of California at Los Angeles, and thewest Los Angeles Veterans Administration Medical Center, Los Angeles, California. Presented at the meeting of the American Laryngological Association, Waikoloa, Hawaii, May 4-5,1991. REPRINTS - Gerald S. Berke, MD, Division of Head and Neck Surgery, UCLA, Le Conte Ave, Los Angeles, CA

2 884 Green et al, Point-Touch Technique ofbotulinum Toxin Injection Location and direction of needle placement for transcutaneous injection of botulinum toxin into ipsilateral thyroarytenoid muscle. A) Through thyroid cartilage. B) Through cricothyroid membrane. A B played a role in others. to They treated these patients successfully with Botox injections. Initial reports of Botox injectionsofthe true vocal fold have relied on EMG localization of the thyroarytenoid musclefor injection. Recently, Fordet alii described an indirect laryngoscopic approach to Botox injection in which all patients studied demonstrated objective improvement after injection. The technique for transcutaneous injection of the vocal fold was first described in connection with Teflon injections as a treatment for unilateral vocal fold paralysis.12ward et al l3 described insertion ofa needle through the cricothyroid membrane into the subglottic space with monitoringof the actual fold injection through a fiberoptic nasopharyngoscope or a Hopkins rod laryngoscope. Hirano et al l4 described a transcutaneous vocal fold injection technique in which the needle is inserted through the cricothyroid membrane directly into the edge of the vocal fold. This report describes a relatively safe and accurate transcutaneous method of Botox injection that requires only flexible nasopharyngeal endoscopy. METHODS AND SUBJECTS Injection Technique. The patient was seated in an examinationchair. Palpationof the neck was used to mark the outline of the thyroid and cricoid cartilage on the anterior neck skin with a surgical marking pen. The nose and pharynx were topically anesthetized with lidocaine 2% spray. A flexible nasopharyngoscope (Olympus, Los Angeles, Calif) was passed through the nose into the hypopharynx to visualize the true vocal folds. The fiberscopic laryngealimage was viewed on a television screen and recorded on videotape. The cutaneous needle injection site was prepared with alcohol. The injection was given with a 2-mL syringe and a 1.5-in 27-gauge needle. The injected material was botulinum A toxin (Oculinum Inc, Berkeley, Calif) that was supplied as a freeze-dried residue ofthe toxin at a concentrationof50 ng per vial (140 U). The freeze-dried toxin was stored at -20 C and reconstituted with 0.9% saline at a concentration of 25 U/mL and used immediately. The injectionwas given throughthe thyroid cartilage into the ipsilateral thyroarytenoid muscle unless the cartilage was ossified (see Figure,A). The needle was orientedat 90 to the skin ofthe neck and directed posteriorly in the sagittal plane. From the previously marked outline of the thyroid cartilage the approximate location of the anterior commissureofthe vocal folds was estimated as midway between the thyroid notch and the bottom edge of the thyroid cartilage, in the midline. IS The needle was placed 5 mm lateral and 5 mm inferior to this point. No previous or concurrent injections of local anesthetic were required. The accuracyof needle placement is assured by pointing the needle, on the basis of anatomic landmarks, into the ipsilateralthyroarytenoidmuscle. The correct depth of needle penetration is judged by sensing the depth at which the needle passesthrough the thyroid cartilageto permiteasy injectionoftoxin. While the needle is within the cartilage, injection pressures are high because of the density of the cartilage matrix. With further penetration, the injection pressure becomes low as the needle enters the thyroarytenoid muscle. We have termed this method the point-touchtechnique. Adequate needle positioning is confirmed through the flexible nasopharyngoscope before injection. Initially, 5 U of toxin was injected bilaterally by the point-touch technique. However, 2 U is routinely given now in order to

3 Green et al, Point-Touch Technique ofbotulinum Toxin Injection 885 INITIAL13 PATIENTS TREATEDBY PERCUTANEOUS BOTOXINJECTION USINGPOINT-TOUCH OR CRICOTHYROID TECHNIQUE Pre/Post Length Previous Glottic of Injection Dose Vocal Response Resistance Pre/Post Patient Symptoms or and Fold Time (cmh20per Jitter Adverse No. (y) Surgery Technique Motion (mo) liter per second) (%) Reactions U bilat PT Normal U bilat PT Bowing 5 69/32 3 Breathy for 2wk U bilat PT Normal Botox 2 U bilat PT Bowing Breathy for 4wk UCT Lfold Breathy for paresis 4wk 6 10 RRLN 4 UR fold, no L fold 6 75/37 section response; 2 U normal Lfold, PT 1 wk later U bilat PT Normal Breathy for 2wk U bilat PT Normal 6 90/50 2 wkbefore improvement 9 5 Botox 2 U bilat PT Normal Botox 1 U bilat PT Normal U bilat PT Normal ULfold CT L fold paralysis 4 70/ U bilat PT Bowing 4 84/40 Breathy for 3wk RLN - recurrent laryngeal nerve, PT - point-touch trans-thyroid cartilage technique, cr- cricothyroid membrane technique. reduce the incidence of vocal fold bowing and breathiness. Ifthe thyroid cartilagecould not be penetratedwith the needle because of ossification, the injection was performed through the cricothyroid membrane (see Figure, B). In this case, the needle was placed just under the edge of the thyroid cartilage, approximately 1.5 em from the midline, and directed superiorly, medially, and posteriorly. The proper depth of penetration and accuracy of needle placement into the ipsilateralthyroarytenoidmuscle were monitored through the flexible nasopharyngoscope. Patients undergoing transcutaneous cricothyroid injection routinely receive 15 U into one vocal fold. Subjects and Evaluation ofvocal Function. During the period April 1990 to October 1991, a total of 13 patients (5 men and 8 women) with a diagnosis of adductor spasmodic dysphonia underwent transcutaneous intrafo1d injection. The Table describes these 13 patients. The length of symptoms varied from 2 years to 10 years. Three of the 13 patients had undergone previous Botox injection with EMG control. One patient had previously undergone a right recurrent laryngeal nerve section. The usual dose for most patients was 2 U. Three patients developed vocal fold bowing after injection, and 2 patients after cricothyroid injection developed a fold paresis or paralysis. Each patient was evaluated by an otolaryngologist and a speech pathologist. Ten of the 13 patients had previously seen a neurologist. Their ages ranged from 32 to 74 years with a mean of50 years. Eleven of 13 patients underwent preinjection vocal function evaluation consisting oflaryngostroboscopy, acoustic analysis of sustained phonation, and laryngeal resistanceestimation. In addition, a l-minutespeech monologue was recorded. Ofthese 13 patients, 4 had acoustic measurements both before and after Botox injection, consisting of jitter of the vowel/a/. Ten of the 13 patients underwent both preinjection and postinjection evaluation of laryngeal resistance by the technique described by Smitheran and Hixon'" with a modification: to reduce the chance that quick fluctuations in phonation influenced the results, we averagedthe amplitudeof the airflow signal over the steady-state, vocalic portion of the syllables, rather than measuring the amplitude of one point in the middle of the syllable. For stroboscopic imaging ofthe larynx, a Bruel & Kjaer laryngostrobe unit (model 4914, Orange, Calif) was used. The stroboscope was connected to a Wolf 90 0 telescope via a fluid-filled light cable. The image was detected by a Toshiba CCD (chargecoupled device) video camera (Toshiba IK-C30A,

4 886 Green et al, Point-Touch Technique ofbotulinum Toxin Injection Buffalo Grove, Ill) and a Sony U-matic videocassette recorder (Sony, VO-9850, Teaneck, NJ). RESULTS Videostroboscopy and Jitter. The preinjection analysis of all 13 patients with adductor spasmodic dysphoniademonstratedcompleteglottic closure with episodes of glottic spasm and supraglotticoverclosure during phonation. The true vocal folds had full symmetric abduction and adduction. All patients demonstrated frequent, intermittent periods of strained vocal quality with occasionalepisodesofaphoniainterrupting speech fluency. Response to the injection lasted from 2 months to 6 months. Perceptually, all 13 patients had an increase in speech fluency and were pleased with the result. Moreover, they have all returned for subsequent injections. The Tablepresents subjectinformation and results after injection. Ourfindings indicate the 95% confidence interval of vocal tract resistance is 37 to 51 cm H20 per liter per second for normally speaking men and 41 to 57 em H20 per liter per second for normally speaking women. (See similar normative results reported by Netsell et al.!") Although normative values for laryngeal resistance varied with sex and age, 10 of the 11 patients evaluated for laryngeal resistance demonstrated elevated laryngeal resistance before injection. Nine of these 10subjects returned to the normal range 4 weeks after injection. The Table also compares the preinjection and postinjection percentjitterfor 4 of the 13injected patients. Threeofthe4patientshadadecreaseinjitter after injection. The one patient with an increase in jitterqualitatively demonstrated a breathy voice, although with increased fluency in continuous speech. The mean preinjection jitter for these 4 patients was 2.08%, comparedto the postinjection value of 0.682%. There were no patients in this group with a posterior glottic chink leak during phonation after injection. Complications. There were no airway complications or infectious complications from this method. All patients, immediately after injection, had a mild degree of true vocal fold edema that resolved. There were no cases of postinjection aspiration. The major adverse reaction includedbreathiness,lasting a maximum of4 weeks in 5 of the 13 patients. One patient noted improvement2 weeks after the injection, rather than the typical 36 hours. DISCUSSION The Botox injections paralyze the thyroarytenoid muscle by blocking the release ofacetylcholine from the presynaptic nerve terminals of the recurrentlaryngeal nerve. Using a caninemodel oflaryngealhyperadduction, Green and Berke 18 have shown that hyperadductioncan be reducedthrough selectivethyroarytenoid muscle paralysis alone. The unilateral absence of thyroarytenoid contraction (despite a vocal fold in the adducted position) allowed the intraglottic and subglottic pressures to fall during phonation. During their initial experience, Miller et al 19 described two patients with unilateral vocal fold adductor paralysis after Botox injection of 20 and 30 U. This was thought to be due to migration of the toxin to the lateral cricoarytenoid muscle. The posterior cricoarytenoid muscle was not affected. Brin et al 20 noticed sluggish vocal fold motion with injection doses of 7.5 U. They were able to achieve selective thyroarytenoid muscle paralysis and reduce the degree of overall fold paralysis by injecting both folds with a reduced dose of 3.75 U. The point-touch technique presented in this report was also able to achieve selective thyroarytenoid muscle paralysis bilaterally with preservation ofvocal fold adduction and abduction. It should be noticed that the three patients who had previously undergone Botox injection using EMG-guided injection underwent injection ofthesame numberofunits using the point-touch technique with the same effective response. This study found subjective perceptual improvements in speech fluency in all patients after injection. Also, all patientsevaluatedbeforeand after injection in this study showed improvement in laryngeal resistance with this technique. In one patient, the improvement in fluency was not accompanied by a decrease in jitter because of an increase in the breathiness of the patient's phonation after injection. This patient was pleased with the result despite the increase in jitter. This problem emphasizes the need to examine a wide variety of speech variables, including measures of continuous speech and pitch breaks, to more fully document patients' speech. The optimal treatment for spasmodic dysphonia, like its fundamental cause, has yet to be found. Until more is known about the disorder, treatments will continue to be directed at the laryngeal symptoms it produces. AlthoughBotox injectionsdo improvethe patient's ability to phonate, the improvement is not permanent. Reinjection is required every 3 to 6 months. The advantages of the transcutaneous injection of Botox are as follows. 1. No EMG equipment or EMG technician is required. 2. The workingdistance is shorterthan the transoral route.

5 Green et al, Point-Touch Technique ofbotulinum Toxin Injection Patients with a sensitive gag reflex or difficulty with full mouth opening can be injected. The disadvantages are as follows: 1. The procedure requires a flexible nasopharyngoscope. 2. A second person is requiredto hold the nasopharyngoscope during injection. 3. In obese patients the external laryngeal landmarks may be difficult to locate. 4. Successful placement of the needle requires a working knowledgeofthe intralaryngealposition of the thyroarytenoid muscle as discerned from external laryngeal landmarks. Efforts have been made to obtain permanentselective bilateral paralysis of the thyroarytenoid muscle surgically. Carpenter et al 21 divided the adductor branch of the recurrent laryngeal nerve in dogs and humans. This procedure was able to preserve the abductor movement ofthe vocal fold, but eliminated the adductor movement, as well as thyroarytenoid muscle contraction. This operation holds out the promise of a permanent selective denervation of the thyroarytenoid muscle. In the interim, the pointtouch technique of Botox injection will allow patients with spasmodic dysphonia to be effectively treated by otolaryngologists within their own communities. REFERENCES 1. Traube L. Spastishe Form der Nervousen Helserkeit. In: 12. SeifertA.PerkutaneParaffininjektionzurBeseitigungder Gesammelte zur Pathologie und Physiologie. Vol 2. Berlin: Folgen Einseitiger Stimmgandlaehmung. Z Laryngol Rhinol Hirschwald, Otol Ihre Grenzgeb 1916;8: Blitzer A, Lovelace RE, Brin MF, Fahn S, Fink ME. 13. Ward PH, Hanson 00, Abemayor E. Transcutaneous Electromyographicfindings in focal laryngeal dystonia (spastic Teflon injection of the paralyzed vocal cord: a new technique. dysphonia). Ann Otol Rhinol LaryngoI1985;94: Laryngoscope 1985;95: Dedo HH. Recurrent laryngeal nerve section for spastic 14. Hirano M, Tanaka S, Tanaka Y, Hibi S. Transcutaneous dysphonia. Ann Otol Rhinol Laryngol 1976;85: intrafold injection for unilateral vocal fold paralysis: functional 4. Izdebski K, Dedo HH, Shipp T, Flower RM. Postoperative results. Ann Otol Rhinol Laryngol 1990;99: and follow-up studies of spastic dysphonia patients treated by 15. KoufmanJA.Laryngoplastyforvocalcordmedialization: recurrent laryngeal nerve section. Otolaryngol Head Neck Surg an alternative to Teflon. Laryngoscope 1986;96: ;89: Smitheran JR, Hixon TJ. A clinical method for estimating 5. Aronson AE, DeSanto LW. Adductor spastic dysphonia: laryngeal airway resistance during vowel production. J Speech three years after recurrent laryngeal nerve section. Laryngoscope Hear Disord 1981;46: ;93: NetsellR,LottsW, DuchaneAS,Barlow SM. Vocal tract 6. BillerHF,SomML,LawsonW.Laryngealnervecrushfor aerodynamics during syllable production: nonnative data and spastic dysphonia. Ann Otol Rhinol LaryngoI1979;88: theoretical implications. J Voice 1991;5: Biller HF, SomML,Lawson W. Laryngeal nerve crush for 18. Green DC, Berke GS. An in vivo canine model for testing spastic dysphonia. Ann Otol Rhinol LaryngoI1983;92:469. treatment effects in laryngealhyperadduction disorders. Laryngoscope 1990;100: Blitzer A, Brin MF, Fahn S, Lange D, Lovelace RE. Letter to the editor. Laryngoscope 1986;96: Miller RH, Woodson GE, Jankovic 1. Botulinum toxin injection of the vocal fold for spasmodic dysphonia. A prelimi- 9. Blitzer A, Brin MF, Fahn S, Lovelace RE. Localized nary report. Arch Otolaryngol Head NeckSurg 1987;113: injections of botulinum toxin for the treatment of focal laryngeal dystonia (spastic dysphonia). Laryngoscope 1988;98: Brin MF, Blitzer A, Fahn S, Gould W, Lovelace RE. Adductor laryngeal dystonia (spastic dysphonia): treatment with 10. Ludlow CL, Naunton RF, Fujita M, Sedory SE. Spas- local injections of botulinum toxin (Botox). Movement Disord modic dysphonia: botulinumtoxin injection after recurrent nerve 1989;4: surgery. Otolaryngol Head Neck Surg 1990;102: Carpenter RJ m,snyder GG m,henley-cohn JL. Selec- 11. Ford CN, Bless DM, Lowery 10. Indirect laryngoscopic tive section of the recurrent laryngeal nerve for the treatment of approachfor injection ofbotulinum toxin inspasmodic dysphonia. spastic dysphonia: an experimental study and preliminary clini- Otolaryngol Head Neck Surg 1990;103: cal report. Otolaryngol Head Neck Surg 1981;89: